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Y Ajioka

Publications and source records attributed to Y Ajioka.

At least 19 recordsLinked to original sources
PubMed1999

Differences in mucus and K-ras mutation in relation to phenotypes of tumors of the papilla of vater.

BACKGROUND: To investigate their hypothesis that K-ras mutation is correlated with epithelial metaplastic change, the authors classified tumors of the papilla of Vater histologically and according to mucin histochemistry as either intestinal type (complete or incomplete) or pancreaticobiliary type (ordinary or metaplastic) and analyzed the tumors for K-ras mutation during tumorigenesis. METHODS: Fifty-two tumors of the papilla of Vater (5 adenomas, 24 carcinomas with adenoma component, and 23 carcinomas) obtained from surgical specimens were evaluated. The mucus phenotype was analyzed with MUC1, MUC2, MUC5AC, sialyl Lewis(a) (CA 19-9), HID-AB, and ConA III stainings. K-ras codon 12 mutation was detected by nested polymerase chain reaction (PCR)-restriction fragment length polymorphism and enriched PCR-enzyme-linked minisequence assay. RESULTS: The presence of adenoma component and intramucosal tumor spreading in the ampulloduodenum was significantly higher in intestinal-type tumors (90%, 27 of 30 tumors, and 100%, 30 of 30 tumors, respectively) than in pancreaticobiliary-type tumors (9%, 2 of 22 tumors, and 23%, 5 of 22 tumors, respectively) (P < 0.0001). MUC2 expression was positive in intestinal-type tumors but not in pancreaticobiliary-type tumors. K-ras mutation rates for incomplete intestinal-type tumors (78%, 7 of 9) and metaplastic pancreaticobiliary-type tumors (64%, 7 of 11), which showed MUC5AC (gastric-type apomucin) expression in cytoplasm, were significantly higher than in complete intestinal-type tumors (33%, 6 of 21) and ordinary pancreaticobiliary-type tumors (18%, 2 of 11) (P = 0.01 and P = 0.03, respectively). In pancreaticobiliary-type tumors, K-ras mutation was more frequently recognized in tumors with ampullopancreatic duct tumor extension (75%, 3 of 4) than in those with ampullobiliary duct extension (0%, 0 of 6) (P = 0.01). Furthermore, sequences of K-ras codon 12 were common in 17 carcinomas with adenoma component that were analyzed for both adenoma and carcinoma. CONCLUSIONS: Tumors of the papilla of Vater can be classified histologically as either intestinal type or pancreaticobiliary type, and they have different features according to tumor location, association with adenoma, and MUC2 expression. Furthermore, K-ras mutation is supposed to be associated with tumors arising in the area from the ampulloduodenum to the ampullopancreatic duct, with metaplastic mucus occurring in both intestinal and pancreaticobiliary types.

Adenoma↗
PubMed1999

Well-differentiated adenocarcinoma mimicking complete-type intestinal metaplasia in the stomach.

We describe extremely well-differentiated intestinal-type adenocarcinomas of the stomach which mimic complete-type intestinal metaplasia. It is often difficult to discriminate such neoplastic lesions from inflamed or regenerative changes of intestinal metaplasia histologically. The aim of this study was to elucidate the clinicopathologic features of this unique carcinoma. Eight cases of gastric carcinoma of this type that were invasive beyond the muscularis mucosae were selected for mucin histochemical and immunohistochemical analyses. The carcinomas showed the following features: (1) predominant cells that had differentiated to mature neoplastic cells, with features of small intestinal absorptive cells (complete-type intestinal metaplastic cells), which have sialomucin, MUC2-positive cells, and brush border features detected by CD10 (56C6) staining; (2) neoplastic tubules in the mucosa showing branching, tortuous, anastomosing, and plexiform structures, which were more pathognomonic than the cytological features; (3) lesions distributed predominantly in the middle third of the stomach and surrounded by the fundic mucosa; and (4) zonal distribution of Ki-67-positive proliferative cells like those of intestinal metaplasia in the lower third to half of the cancerous tubules in the mucosa. The lesions consisted mainly of illusory carcinoma; however, there were foci of pathognomonic elements in some areas of the tumors. Several biopsy samplings of the lesion would ensure the histopathologic diagnosis. This unique lesion forms a subgroup of intestinal-type carcinomas of the stomach and is suggested to have a close link with complete-type intestinal metaplasia, previously ignored as a precancerous lesion.

Adenocarcinoma↗
PubMed1999

DNA microsatellite instability in hyperplastic polyps, serrated adenomas, and mixed polyps: a mild mutator pathway for colorectal cancer?

AIM: To investigate the distribution of DNA microsatellite instability (MSI) in a series of hyperplastic polyps, serrated adenomas, and mixed polyps of the colorectum. METHODS: DNA was extracted from samples of 73 colorectal polyps comprising tubular adenomas (23), hyperplastic polyps (21), serrated adenomas (17), and mixed polyps (12). The presence of MSI was investigated at six loci: MYCL, D2S123, F13B, BAT-40, BAT-26, and c-myb T22, using polymerase chain reaction based methodology. MSI cases were classified as MSI-Low (MSI-L) and MSI-High (MSI-H), based on the number of affected loci. RESULTS: The frequency of MSI increased in tubular adenomas (13%), hyperplastic polyps (29%), serrated adenomas (53%), and mixed polyps (83%) (Wilcoxon rank sum statistic, p < 0.001). Hyperplastic epithelium was present in nine of 12 mixed polyps and showed MSI in eight of these. MSI was mostly MSI-L. MSI-H occurred in two serrated adenomas and three mixed polyps. Clonal relations were demonstrated between hyperplastic and dysplastic epithelium in four of eight informative mixed polyps. CONCLUSIONS: The findings support the view that hyperplastic polyps may be fundamentally neoplastic rather than hyperplastic. A proportion of hyperplastic polyps may serve as a precursor of a subset (10%) of colorectal cancers showing the MSI-L phenotype, albeit through the intermediate step of serrated dysplasia. This represents a novel and distinct morphogenetic pathway for colorectal cancer.

Adenoma↗
PubMed1999

Immunohistochemical staining patterns of MUC1, MUC2, MUC4, and MUC5AC mucins in hyperplastic polyps, serrated adenomas, and traditional adenomas of the colorectum.

We studied the distribution of the four human apomucins MUC1, MUC2, MUC4, and MUC5AC in hyperplastic polyps, serrated adenomas, and traditional adenomas of the colorectum using immunohistochemical techniques, with the aim of comparing and contrasting their patterns of expression. A series of 12 hyperplastic polyps, 27 serrated adenomas, and 20 traditional adenomas was studied. No significant change in apomucin expression was observed in traditional adenomas compared with normal colorectal epithelium, except for MUC5AC, which was present in 12 of the adenomas (60%) and only 20% of the normal samples. In both hyperplastic polyps and serrated adenomas, MUC2 and MUC5AC mucin expression was consistently and markedly increased. In 50% of the hyperplastic polyps, MUC4 was reduced but in the remaining cases was similar to normal. Loss of MUC4 expression was observed in all serrated adenomas. MUC1 was not increased in the hyperplastic polyps but increased expression was seen in 17 of the serrated adenomas (63%). Similar altered distribution patterns of MUC2, MUC4, and MUC5AC were seen in hyperplastic polyps and serrated adenomas, whereas traditional adenomas showed little change from normal patterns of expression. Although hyperplastic polyps are commonly defined as benign lesions without neoplastic potential, the similar phenotypes of hyperplastic and serrated adenomas and the existence of mixed polyps suggest that these lesions may represent a histogenetic continuum.

Adenoma↗
PubMed1999

Histological and genetic changes in malignant transformation of gallbladder adenoma.

DESIGN: Elucidate the histological and genetic changes in malignant transformation of adenoma of the gallbladder. MATERIALS AND METHODS: Forty-three adenomas and 20 intramucosal tumors of carcinoma-in-adenomas were studied for histological and genetic changes (particularly K-ras mutation and p53 protein overexpression by immunohistochemistry) in malignant transformation. The genetic changes were compared with those of 164 carcinomas without anomalous union and 17 carcinomas with anomalous union of pancreatico-biliary duct. RESULTS: Atypical cell foci, i.e. spindle cell foci, were observed only in the adenoma area, with a frequency of 23% in 39 adenomas, and of 45% in 20 tumors of carcinoma-in-adenoma. 129 of 130 spindle cell foci examined were negative for Ki-67 staining and all the spindle cell foci were negative for p53 stain. K-ras mutation and p53 overexpression were not found in all adenomas, pure and with carcinoma i.s., and only one carcinoma (1/16, 6%) with adenoma showed p53 overexpression. K-ras mutation was low (10%, 4/40) in carcinomas without adenoma, but high in carcinomas with anomalous union of pancreatico-biliary duct. While, p53 overexpression was high and similar in carcinomas with and without anomalous union. CONCLUSIONS: These results suggest that there are three distinct pathways in gallbladder carcinogenesis; that is, de novo carcinoma develops from a predominant p53 alteration with low K-ras mutation, de novo carcinoma with anomalous union from K-ras mutation and p53 mutation, and carcinoma-in-adenoma from K-ras-, p53-, and probably APC-gene-related, as yet unknown, alteration.

Adenoma↗
PubMed1998

Determination of pancreatic ductal carcinoma histogenesis by analysis of mucous quality and K-ras mutation.

BACKGROUND: The authors sought to elucidate the histogenesis of pancreatic ductal carcinoma by correlating K-ras mutation with mucus type in normal epithelium, mucous cell hyperplasia (MCH), and carcinoma. METHODS: Seventy-four solid-type carcinomas (SCs), 23 ductectatic-type carcinomas (DCs), and specimens of 24 normal pancreata were studied. By histochemical staining, normal duct epithelia, areas of MCH, and carcinomas were classified as having sulfo-type or sialo-type mucus. Foci from normal, DC, SC, sulfo-type, or sialo-type specimens were assessed for K-ras mutation at codon 12 by nested polymerase chain reaction and restriction fragment length polymorphism. RESULTS: Of the SCs, 9 were sulfo-type and 65 were sialo-type; all DC specimens were sialo-type, and all normal epithelia were sulfo-type. All foci of sulfo-type, nonneoplastic epithelia were negative for K-ras mutation. In contrast, 124 of 313 sialo-type MCH foci (40%) had a K-ras mutation. Of 74 SCs, only 3 of 9 sulfo-type tumors (33%) were positive for the mutation. Sixty of 65 sialo-type SCs (92%) had a K-ras mutation, whereas 15 of 23 sialo-type DCs (65%) had a mutation. K-ras mutant carcinomas (including both SCs and DCs) were associated with K-ras mutant MCH in 109 of 198 MCHs (55%), whereas carcinomas without a K-ras mutation had mutations in 6 of 68 MCHs (9%). MCH in normal pancreata revealed K-ras mutations in 9 of 51 foci (18%). In addition, in K-ras mutant carcinomas, frequency of K-ras mutation in MCH increased from 27% (11 of 41 foci) of nonpapillary MCHs to 62% (98 of 157 foci) of papillary MCHs; but in K-ras wild-type carcinoma, the mutation rate in MCH was unchanged from 12% (3 of 26 foci) to 7% (3 of 42 foci) in nonpapillary and papillary foci, respectively. CONCLUSIONS: These results suggest a strong relationship between the risk of pancreatic carcinoma and the presence of combinations of K-ras gene mutation, papillary growth, and expression of sialomucin in foci of MCH.

Adult↗
PubMed1998

Advantages of immunostaining over DNA analysis using PCR amplification to detect p53 abnormality in long-term formalin-fixed tissues of human colorectal carcinomas.

To study the appropriate period for formalin fixation in order to detect p53 abnormalities in formalin-fixed tissue, we used seven surgically resected human colorectal cancer specimens. The immunohistochemical reactivity of p53 immunostaining and amplification of DNA by polymerase chain reaction (PCR) of the p53 gene were compared after various periods of 10% formalin fixation (1 day, and 1, 2, 4, and 8 weeks). For comparative immunostaining, we used the monoclonal antibody Ki-67 (MIB-1), and for comparative polymerase chain reaction (PCR), K-ras at codon 12 was amplified. Immunostaining was performed by the streptavidin-biotin method with microwave retrieval, and PCR amplifications were performed by the nested PCR method. p53 and Ki-67 immunoreactivity did not change essentially for up to 2 weeks and 1 week, respectively, of formalin fixation. PCR amplification for p53 at exon 8 and K-ras at codon 12 was successful until 1 day and 2 weeks, respectively, of formalin-fixation for the specimens of all seven cases. Thereafter, the amplification tended to worsen as the fixation time lengthened. Further, the DNA was more successfully amplified in the second PCR than in the first. These results suggest that to detect p53 abnormality in specimens that have been formalin-fixed for long periods, immunohistochemical staining may have advantages over DNA analysis with PCR amplification.

Colorectal Neoplasms↗
PubMed1998

Immunoperoxidase staining for cytokeratins 8 and 18 is very sensitive for detection of occult node metastasis of colorectal cancer: a comparison with genetic analysis of K-ras.

AIMS: Recent reports suggest that genetic examination of K-ras or p53 mutation is more sensitive for the detection of occult lymph node metastasis in colorectal carcinomas than conventional examination by haematoxylin and eosin (H & E) staining or immunohistochemistry for gene products. The aim of this study was, first, to define the microscopic characteristics of metastatic cancer cells in lymph nodes stained by the anti-cytokeratin antibody CAM5.2 for cytokeratins 8 and 18, and, second, to compare the detection rate of occult lymph node metastasis for immunohistochemical vs genetic methods. METHODS AND RESULTS: K-ras mutations were first examined in primary tumours of seven cases which showed distant metastasis or local recurrence within 5 years of the initial surgery in spite of the original reporting of no lymph node metastasis by routine H & E staining. K-ras mutations were positive in three cases in primary tumours and lymph nodes, and the remaining four primary tumours were negative for p53 mutation as well as K-ras mutation. Therefore, genetic analysis of occult lymph node metastasis was uninformative, but occult metastasis was detected by cytokeratin staining in two of these four cases. Comparative study of cytokeratin-positive cells was performed on each of the 43 lymph nodes from three cases with K-ras mutations. Cancer cells were detected in 28 of the 43 lymph nodes (65.1%) by cytokeratin staining and in 10 of the 43 corresponding lymph nodes (23.3%) by genetic analysis. Artefactual contamination by cancer cells was present in eight of the 28 cytokeratin positive lymph nodes, and three of the eight nodes were genetically positive. CONCLUSIONS: This study suggests that cytokeratin immunohistochemistry is more sensitive and specific for the detection of occult lymph node metastasis than genetic diagnosis by K-ras mutation in cases with genetic alterations as well as in cases without them.

Aged↗
PubMed1998

Alteration of p53 clonality accompanying colorectal cancer progression.

The aim of this study was to clarify whether or not the status of gene alteration is heterogeneous in intramucosal carcinoma and homogeneous within invasive carcinoma. We selected 10 colorectal carcinoma cases (1 mucosal, 5 submucosal and 4 advanced carcinomas including 2 cases with lymph node metastasis) and analyzed the p53 gene sequence. Six colorectal cancers in this study showed heterogeneity in p53 mutations in cells from the intramucosal part. In the invasive part of a carcinoma, p53 mutation status was homogeneous intratumorally in all cases. These data indicate that, in regard to p53 gene alterations, colorectal cancers can be composed of various subclones when limited to the mucosa, but clonal selection occurs when one of these subclones commences invasion to the submucosa, generating a monoclonal invasive carcinoma.

Adenoma↗
PubMed1998

Heterogeneity of p53 mutational status in esophageal squamous cell carcinoma.

In esophageal squamous cell carcinoma, p53 gene mutations have been analyzed for inter- or intra-patient heterogeneity but only a few studies have investigated intratumoral heterogeneity. We investigated this question within individual esophageal cancers, and also in their lymph-node metastases in 8 cases. Analyzing the p53 gene sequence by direct sequencing of polymerase chain reaction products, we found heterogeneity for p53 mutations in the pre-invasive area in 3 esophageal cancers. In all areas sampled in the invasive portion of each cancer, the p53 mutational status was identical in a given tumor. In heterogeneous tumors, the invasive area showed one of the p53 mutations found in the pre-invasive area. In nodal metastases, the p53 mutation was identical to that in the invasive area of each primary tumor. These data suggest that the timing of p53 alteration is not as early as might have been expected, indicating that, in regard to p53 gene alteration, some esophageal cancers are composed of various subclones in the pre-invasive stage with invasiveness developing in one of them, which becomes predominant through clonal selection.

Aged↗
PubMed1998

Infrequent K-ras codon 12 mutation in serrated adenomas of human colorectum.

BACKGROUND: Serrated adenoma is a new morphological subtype of colorectal adenoma. The lesion provides a distinct morphological route to carcinoma, but the underlying genetic changes have not yet been investigated. AIMS: To determine the frequency of K-ras mutation in serrated adenoma. METHODS: The frequency of K-ras codon 12 point mutation in 20 serrated adenomas, five atypical hyperplastic polyps, and 58 sporadic polypoid adenomas was investigated by nested polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. RESULTS: Although most of the serrated adenomas were large (average size 11.4 mm) and polypoid, K-ras codon 12 point mutation was detected in only one of the 20 (5%), which is a significantly lower frequency than that in sporadic polypoid adenomas (18/60; 30%) (p = 0.017). No mutation was detected in the atypical hyperplastic polyps. Three of 20 (15%) serrated adenomas contained a focus of carcinoma in situ, indicating their malignant potential and the existence of a serrated adenoma-carcinoma sequence, but no mutation was detected in the foci of carcinoma in situ. CONCLUSIONS: K-ras mutation is uncommon in serrated adenomas, indicating a different spectrum of genetic alterations in these lesions from those in typical polypoid sporadic adenomas. This subtype of colorectal adenoma represents a new genetic pathway in the histogenesis of colorectal carcinoma.

Adenoma↗
PubMed1998

[The autopsy case of traumatic carotid artery dissection].

The results of an autopsy of a 78-year-old female patient with an occluded of the right internal carotid artery after a traffic accident are reported. She presented with consciousness disturbance, right conjugate deviation, left hemiparesis and left pathological reflex. Evidence of right skull and clavicular fractures seemed to suggest that severe hyperextension of her neck associated with contralateral lateral flexion had stretched her carotid artery. Although she was treated with antiplatelet therapy, her cerebral swelling due to right global infarction progressed and she died due to bilateral cerebral herniation three days after injury. The autopsy disclosed right dissecting carotid artery occlusion and subadventitial dissection was revealed histologically. When a hematoma dissect the media and adventitia of the carotid artery wall, the outer wall weakens and may dilate without narrowing the lumen of the carotid artery. In this case, the vessel occlusion was considered to be due to a primary intramural hematoma which developed and subsequently ruptured through the intima into the vessel lumen. Early diagnosis and treatment are necessary for improving the prognosis of this disease entity. A patient with poor colateral flow, such as in this case, will show a rapid progression of cerebral infarction. It is best to consider surgical treatment in this case if the other traumatic lesions are able to tolerate surgery.

Aged↗
PubMed1998

Mutations of p53 in gallbladder carcinomas in high-incidence areas of Japan and Chile.

Gallbladder adenocarcinomas from patients in two high-prevalence areas, Niigata (Japan) and Santiago (Chile), were analyzed for acquired mutations in exons 5-8 of the p53 tumor suppressor gene, and the characteristics of p53 alterations in the two groups were compared. Of 42 tumors, 22 (52.4%) harbored 25 alterations identified by PCR amplification and direct sequencing (13 of 22 tumors from Niigata and 12 of 20 tumors from Santiago). All alterations were single base pair substitutions, 20 (80%) leading to an amino acid substitution or a chain-termination signal, and 5 (20%) were silent. Immunohistochemically, 55 of 84 cases (65.5%) showed overexpression of p53 protein, with no significant difference in frequency between the two areas. Missense mutations correlated highly with overexpression of the p53 protein (93.4%). Mutations of p53 occurred in all four exons examined, most commonly in exon 5, but in no particular "hot spot." In base-change spectra, all 12 mutations from Santiago showed transitions, with 4 arising at the CpG dinucleotide (33.3%). In contrast, no such transition was found at CpG sites in Niigata, and 4 of 13 mutations (30.8%) were transversions. The data indicated that p53 mutations are highly important in carcinogenesis in the gallbladder. In addition, the difference in p53 mutational spectra in Niigata and Santiago indicate a likely regional difference in mutagenesis.

Adult↗
PubMed1998

[Genetic alterations in gallbladder carcinoma: a review].

Earlier evidence suggests that gallbladder carcinoma (GBC) has three carcinogenic pathways; de novo development; adenoma-carcinoma sequence; and hyperplasia-carcinoma sequence associated with an anomalous arrangement of the pancreaticobiliary duct (AAPBD). We review gene abnormalities in GBC reported to date. p53 mutation and its protein overexpression are frequently observed in de novo carcinoma and GBC with AAPBD, but never found in carcinoma with adenoma. The incidence of K-ras codon 12 mutation in GBCs with AAPBD is significantly higher than that in the other types. Mutation of K-ras is never detected in carcinoma with adenoma. These findings suggest that diverse genetic pathways may exist in gallbladder carcinogenesis and reflect morphologic variations.

Adenoma↗
PubMed1997

Macroscopic and stereomicroscopic diagnosis of superficial flat-type early carcinomas of the gallbladder.

Superficial flat early carcinomas of the gallbladder are rarely detected clinically. We previously reported that these carcinomas display granular, flat, or gastric area-like surface mucosal patterns. However, these patterns are also seen in some non-neoplastic conditions. To more definitively differentiate carcinomas from non-neoplastic lesions, we analyzed the stereomicroscopic structure of macroscopically granular, flat, or gastric area-like mucosal lesions with a methylene-blue contrast technique. Sixteen superficial flat early carcinomas and 65 non-neoplastic flat lesions from surgically resected gallbladders were studied by stereomicroscopy. The fine mucosal structures were classified into three patterns: grooved, pitted, or papillary, each of which was further subdivided into regular and irregular. The frequency of the grooved (52.2%) and papillary (52.2%) patterns was significantly higher in the carcinomas than in the non-neoplastic lesions (24.7% and 1.3%, respectively). The pitted pattern was present in 69.6% of the carcinomas and in 53.2% of the non-neoplastic lesions (the difference was not significant). In the grooved and pitted patterns, the irregular subtypes predominated in the carcinomas (100% and 81.3%, respectively), while the regular subtypes were more frequent in the non-neoplastic lesions (84.2% and 97.6%, respectively). Stereomicroscopic examination of the fine mucosal structures of flat lesions of the gallbladder is very useful in differentiating carcinomas from non-neoplastic lesions.

Adenocarcinoma↗
PubMed1997

Occult lymph node metastases detected by cytokeratin immunohistochemistry predict recurrence in "node-negative" colorectal cancer.

There is controversy about the prognostic significance of occult lymph node metastases detected by immunohistochemistry with the anti-cytokeratin antibody CAM 5.2. The aim of this study was to characterize occult lymph node metastases in colorectal carcinomas that might be associated with a higher risk of recurrence. Three hundred fifty-eight lymph nodes from 10 recurrent and 9 nonrecurrent cases of colorectal carcinoma were examined. All these patients had been reported originally as having no lymph node metastases by routine hematoxylin and eosin staining. Three 10-micron sections or ten 3-micron sections (30-micron total thickness) from each lymph node were stained with CAM 5.2 and examined for the presence of occult lymph node metastases. Occult metastases were detected in 67 of 175 lymph nodes from the recurrent cases, and in 23 of 183 lymph nodes from the nonrecurrent cases. The frequency of positive nodes was significantly higher in the recurrent cases. The recurrent cases had metastases in nodes more distant from the main tumor than did the nonrecurrent cases. Detection of occult lymph node metastases with cytokeratin immunohistochemistry may make it possible to identify patients with a higher risk of recurrence after the removal of a primary colorectal tumor.

Adult↗